The legal and ethical dilemma of embryonic stem cells: an impediment to translation in medicine? E. Rial-Sebbag, A. Mahalatchimy, A.M. Duguet

The legal and ethical dilemma of embryonic stem cells: an impediment to translation in

medicine?

E. Rial-Sebbag, A. Mahalatchimy, A.M. Duguet

Helex, 23rd-25th June, Oxford 2

Outline

• Talking about hESC.• Talking about patenting hESC:

– Brustle Case– Isco Case

• Impact on research pathways.• Impact on research strategies.


http://www.medexpressrx.com/research/treatments-of-diseases.aspx


Induced Pluripotent Stem cells

http://learn.genetics.utah.edu/content/stemcells/quickref/


Regenerative medicine

• “Regenerative medicine is an interdisciplinary field of research and clinical applications focused on the repair, replacement or regeneration of cells, tissues or organs to resort impaired function resulting from any cause, including congenital defects, disease, trauma and ageing. It uses a combination of several converging technological approaches, both existing and newly emerging, that moves it beyond traditional transplantation and replacement therapies. The approaches often stimulate and support the body’s own self healing capacity” [Daar AS, Greenwood HL, 2007].‐


Why Human embryonic stem cells are so important?

• Immature cells.

• High capacity of diferenciation.

• Accessible since progress in fertilization (IVF).


Why using hESC is so problematic?

• Shared ethical principles– Cells of human origin (anthropological approach) ;– Research on hESC implies the destruction of the

embryo or the impossibility to reimplant the embryo;

– Infringement of the Right to Life (European Convention on Human Rights, article 2) ;

– Sometimes it is considered as immoral.


But….

• Heterogeneous legal responses in Europe– Research is banned (Germany, Italy)– Research is authorised under conditions (France,

UK)– Research is banned but with exemptions (France

before 2011)

• How to translate knowledge in hESC to clinics and to the market ?


hESC Research

• Is increasing in Europe ;

• Is limited by enforceable regulations ;

• Is challenged by the public opinion in the various countries.


Europeans and Biotechnology in 2010 Winds of change?


PatentabilityDirective 98/44/EC

• Protection of the innovation through patentability (Confer the right to exclude others from making, using, or selling the claimed invention).

• Patentability criteria: novelty of the invention, inventive step, industrial application, respect ordre public or morality.

Helex, 23rd-25th June, Oxford

Industrial and commercial use of human embryos

• CJEU: Case law Oliver Brüstle / Greenpeace Ev ( C-34/10), 18 October 2011– Mr Oliver Brüstle: holder of a patent on precursor cells

produced from ESC to treat neurological diseases– On application by Greenpeace Ev, the German Federal

Patent Court ruled: invalid patent as it covers processes for obtaining precursor cells from human ESC

– Mr Brüstle’s appeal– German Federal Court of Justice refers questions to the

CJEU on the interpretation of Directive 98/44/EC

12


CJEU: Case law Oliver Brüstle18 October 2011

• Three questions referred for a preliminary ruling:1) What is meant by the term « human embryo »?2) What is meant by the expression “uses of human embryos for industrial or commercial purposes”? 3) No patentability because of prior destruction of human embryos, or because of their use as base material?

13



• 1) What is meant by the term « human embryo »?– Wide meaning: « any human ovum after fertilisation,

any non-fertilised human ovum into which the cell nucleus from a mature human cell has been transplanted and any non-fertilised human ovum whose division and further development have been stimulated by parthenogenesis”

– Return to the referring court: “to ascertain, in the light of scientific developments, whether a stem cell obtained from a human embryo at the blastocyst stage constitutes a ‘human embryo’”

14



• 2) What is meant by the expression “uses of human embryos for industrial or commercial purposes”?

– The exclusion of patentability covers use for purposes of scientific research

15



• 3) No patentability because of prior destruction of human embryos, or because of their use as base material?– Both– an invention is excluded from patentability “where

the technical teaching which is the subject-matter of the patent application requires the prior destruction of human embryos or their use as base material”

16


JUDGMENT OF THE COURT (Grand Chamber)18 December 2014

International Stem Cell Corporation


The legal question

Article 6(2)(c) of Directive 98/44 must be interpreted as meaning that an unfertilised human ovum whose division and development to a certain stage have been stimulated by parthenogenesis constitutes a ‘human embryo’ within the meaning of that provision?

18


The decision

• an unfertilised human ovum whose division and further development have been stimulated by parthenogenesis does not constitute a ‘human embryo’, within the meaning of that provision, if, in the light of current scientific knowledge, it does not, in itself, have the inherent capacity of developing into a human being, this being a matter for the national court to determine.


Criteria for patenting

-Does the patent suggest or refer to the use of a “human embryo”? - the inherent capacity of developing into a human

being.-Does the patent involve the destruction of a “human embryo”?


Consequences for research pathways

• Sustainability of research if private companies can invest.

• Reinforcement of public/private partnerships.

• Collaborations enforced through Stem cell banks.


Consequences for research strategies

• Companies will naturally go where they can protect their discoveries ;

• Will impact on the choice to invest in one or another technique;

• Will imply to make the information on the tecnhique used to derive cells lines (with or without destruction of the embryo) available in cell lines registries.


Mahalatchimy A. and al., The impact of European embryonic stem cell patent decisions on research strategies.


To conclude

• Field of Stem cell is quite difficult to frame in a context of concurrent initiatives (elaboration of scenarios);

• Part of the decision to invest in one or the other field is the “return of investment” mostly constituted by the protection offered by patents;

• Change of the Court position will probably reassure the companies to develop new fertilisation methods but will lead to other forms of bioethical questioning on procreation.

• It encourages companies to stay or to come to Europe to benefit from this patents 'regime.


Further issues…

• Node of confusion between patentability (property right) and commercialisation of the human body (Fundamental rights).

• Still an effort to make for avoiding the “pollution” of the discourse around stem cells by the bioethical questions posed by hESC.

• Use of IPS cell lines is seen as an alternative BUT the techniques are not scientifically equivalent and IPS should raise issues.

Helex, 23rd-25th June, Oxford 26http://ec.europa.eu/public_opinion/archives/quali/ql_futureofscience_en.pdf

- In some countries stem cell research was not well understood by all (NL, CZ,EE, PT, SK), but when it was understood most participants in all countries likedthe idea of stem cell therapy for organ repair. Reasons for liking it includedthat this method will be able to cure many diseases.- Reservations focused on ethical concerns (whether people should change natureor let it run its course), cost and whether people will become careless with theirhealth because they know they can be cured with stem cell therapy.


THANK [email protected]

This work has been partly supported by the EUceLEX project (FP7, GA: NO: 601806)

Documents

The legal and ethical dilemma of embryonic stem cells: an impediment to translation in medicine? E. Rial-Sebbag, A. Mahalatchimy, A.M. Duguet